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  • Buchebner, David, et al. (författare)
  • Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality
  • 2017
  • Ingår i: Endocrine Pathology. - Humana Press. - 2472-1972. ; 1:6, s. 615-624
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear.Objective: To describe normal PTH profiles over time and the association with mortality.Design and Participants: There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years).Main Outcome Measures: PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality.Results: At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082).Conclusions: Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old.
  • Grundberg, Elin, et al. (författare)
  • The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism.
  • 2007
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 92:6, s. 2300-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ER -cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ER alpha function in the presence of estrogen. Objective: The objective of the study was to determine whether a RIZ P704 insertion (+)/ deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. Design: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmo OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmo University Hospital, and Uppsala University Hospital. Participants: In total, 4058 men and women, aged 69 -81 yr, were randomly selected from population registries. Main Outcome Measures: BMD(grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. Results: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(+/+) group (r = 0.19 vs. r = 0.08, P < 0.05). Conclusions: These large-scale studies of elderly men and women indicate that the ER alpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.
  • Gyllenberg, Alexandra, et al. (författare)
  • Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
  • 2012
  • Ingår i: Genes and Immunity. - Nature Publishing Group. - 1476-5470. ; 13:8, s. 632-640
  • Tidskriftsartikel (refereegranskat)abstract
    • The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
  • Lagerholm, Sofia, et al. (författare)
  • Genetic Regulation of Bone Traits Is Influenced by Sex and Reciprocal Cross in F-2 Progeny From GK and F344 Rats
  • 2009
  • Ingår i: Journal of Bone and Mineral Research. - AMBMR. - 1523-4681. ; 24:6, s. 1066-1074
  • Tidskriftsartikel (refereegranskat)abstract
    • A genome-wide linkage analysis to identify quantitative trait loci (QTLs) for bone phenotypes was performed in an F-2 intercross of inbred spontaneously type 2 diabetic GK and normoglycemic F344 rats (108 males and 98 females). The aim of the study was to locate genome regions with candidate genes affecting trabecular and cortical bone and to investigate the effects of sex and reciprocal cross. pQCT was used to determine tibia] bone phenotypes in the F2 rats, comprising reciprocal crosses with divergent mitochondrial (mt) DNA. Sex and reciprocal cross-separated QTL analyses were performed followed by assessment of specific interactions. Four genome-wide significant QTLs linked to either cortical vBMD, tibia length, body length, or metaphyseal area were identified in males on chromosomes (chr) 1, 8, and 15. In females, three significant QTLs linked to cortical BMC or metaphyseal total vBMD were identified on chr 1 and 2. Several additional suggestive loci for trabecular and cortical traits were detected in both males and females. Four female-specific QTLs on chr 2, 3, 5, and 10 and four reciprocal cross-specific QTLs on chr 1, 10, and 18 were identified, suggesting that both sex and mt genotype influence the expression of bone phenotypes. J Bone Miner Res 2009;24:1066-1074. Published online on December 29, 2008; doi: 10.1359/JBMR.081252
  • Swanberg, Maria, et al. (författare)
  • Polymorphisms in the macrophage migration inhibitory factor gene and bone loss in postmenopausal women.
  • 2010
  • Ingår i: Bone. - 1873-2763. ; 47:2, s. 424-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis is a severe condition in postmenopausal women and a common cause of fracture. Osteoporosis is a complex disease with a strong genetic impact, but susceptibility is determined by many genes with modest effects and environmental factors. Only a handful of genes consistently associated with osteoporosis have been identified so far. Inflammation affects bone metabolism by interfering with the interplay between bone resorption and formation, and many inflammatory mediators are involved in natural bone remodeling. The cytokine macrophage migration inhibitory factor (MIF) has been shown to affect bone density in rodents, and polymorphisms in the human MIF promoter are associated with inflammatory disorders such as rheumatoid arthritis. We investigated the association of polymorphisms in the MIF gene with bone mineral density (BMD) and bone loss in 1002 elderly women using MIF promoter polymorphisms MIF-CATT(5)(-)(8) and rs755622(G/C) located -794 and -173bp upstream of the transcriptional start site. Bone loss was estimated both by the change in BMD over 5years and by the levels of bone resorption markers in serum measured at four occasions during a 5-year period. The MIF-CATT(7)/rs755622(C) haplotype was associated with increased rate of bone loss during 5years at the femoral neck (p<0.05) and total hip (p<0.05). In addition, the MIF-CATT(7)/rs755622(C) haplotype carriers had higher levels of the bone turnover marker serum C-terminal cross-linking telopeptide of type I collagen (S-CTX-I, p<0.01) during the 5year follow-up period. There was no association between MIF-CATT(7)/rs755622(C) and baseline BMD at femoral neck, total hip or lumbar spine. We conclude that MIF promoter polymorphisms have modest effects on bone remodeling and are associated with the rate of bone loss in elderly women.
  • Berggren, Lars, et al. (författare)
  • Studiemedel för studiero
  • 2014
  • Ingår i: Helsingborgs Dagblad. - Helsingborgs Dagblad. - 1103-9388.
  • Tidskriftsartikel (populärvet., debatt m.m.)
  • Berglundh, Sofia, et al. (författare)
  • C-reactive protein, bone loss, fracture, and mortality in elderly women: a longitudinal study in the OPRA cohort.
  • 2015
  • Ingår i: Osteoporosis International. - Springer. - 1433-2965. ; 26:2, s. 727-735
  • Tidskriftsartikel (refereegranskat)abstract
    • This longitudinal study investigates the association between C-reactive protein (CRP), osteoporosis, fractures, and mortality in 1044 elderly women. CRP was not an indicator for low bone mineral density (BMD), bone loss, or fracture in elderly women; however, women with elevated CRP levels over a prolonged period lost more bone over the 10-year follow-up, although fracture risk was not increased.
  • Bobjer, Johannes, et al. (författare)
  • High Prevalence of Hypogonadism and Associated Impaired Metabolic and Bone Mineral Status in Subfertile Men.
  • 2016
  • Ingår i: Clinical Endocrinology. - Wiley-Blackwell. - 1365-2265. ; 85:2, s. 189-195
  • Tidskriftsartikel (refereegranskat)abstract
    • It is yet unknown to which degree young subfertile men present with signs of hypogonadism and whether low testosterone concentration, like in older men, is associated with risk of osteoporosis and metabolic derangements in those subjects. The objective was, therefore, to investigate the prevalence of hypogonadism and its association with metabolic and bone parameters in young subfertile men.
  • Book, Christina, et al. (författare)
  • Changes in body composition after 2 years with rheumatoid arthritis
  • 2011
  • Ingår i: Scandinavian Journal of Rheumatology. - Taylor & Francis. - 1502-7732. ; 40:2, s. 95-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Rheumatoid arthritis (RA) is associated with cardiovascular disease (CVD). Possible predictors for CVD are early changes in body composition. We therefore evaluated changes in lean body mass (LBM), lean mass of arms and legs (LMAL), total body fat mass (BFM), and truncal fat distribution (FD) after 2 years with RA and possible predictors. Methods: We registered 63 (45 women) RA patients with disease duration of <= 12 months at baseline and after 2 years. Disease Activity Score using 28 joint counts (DAS28), Health Assessment Questionnaire (HAQ) score, body mass index (BMI), comorbidities, smoking, and medications were recorded. Total and regional lean mass and fat mass were measured with dual energy X-ray absorptiometry (DXA). The data were compared with 63 age- and gender-matched controls. Results: LBM and LMAL at baseline in RA patients were significantly lower in men (p = 0.020 and 0.002, respectively) compared to matched controls. Truncal FD was non-significantly increased in RA patients (women p = 0.133, men p = 0.119). The age-related deterioration with decreased LBM after 2 years (p = 0.002 in women and men) and increased BFM (p < 0.001) and truncal FD (p = 0.020) in women were all significantly less pronounced in RA patients than in matched controls. Conclusions: In patients with early RA and after initiation of therapy, the age-related deterioration with decreasing LBM and increasing truncal FD was lower than in control subjects in this observational study. These potentially harmful alterations seem to be modifiable factors in patients with early RA.
  • Book, Christina, et al. (författare)
  • Disease activity and disability but probably not glucocorticoid treatment predicts loss in bone mineral density in women with early rheumatoid arthritis
  • 2008
  • Ingår i: Scandinavian Journal of Rheumatology. - Taylor & Francis. - 1502-7732. ; 37:4, s. 248-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Osteoporosis is a known complication of rheumatoid arthritis (RA). This prospective study aimed to evaluate whether disease activity, disability, and glucocorticoid (GC) treatment in early RA were risk factors for loss of bone mineral density (BMD). Methods: We followed 97 women (mean age 58 years), for 24 months, with a history of RA of less than 12 months. At baseline, 77 women were receiving standard treatment with disease-modifying antirheumatic drugs (DMARDs) and 20 were receiving no treatment. Risk factors for osteoporosis were recorded. Disease activity score (DAS28), Health Assessment Questionnaire (HAQ) score, and medications were registered at baseline and every 6 months and calculated as areas under the curve (AUCs). Femoral neck and lumbar spine BMD were measured at baseline and after 2 years and compared to BMD in age- and gender-matched controls. Risk factors were analysed by linear regression models. Results: BMD loss was comparable to that of age-matched women in both the lumbar spine and the femoral neck, although neither was significantly different from baseline. In multivariate analyses the AUC for DAS28 was an independent predictor of changes in lumbar spine BMD (p=0.003) and that for HAQ of changes in femoral neck BMD (p=0.018). GC use was not an overall predictor of BMD loss. Conclusion: BMD loss was predicted by high disease activity and disability but not by GC treatment. With the DMARD, GC, hormone replacement therapy (HRT), and bisphosphonate treatment strategies used during the study period, the general outcome seems favourable concerning loss of BMD in patients with early RA.
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